36 genes linked to heart failure identified

Sun Online Desk
12th March, 2018 10:23:04

Scientists have identified 36 new genes linked to heart failure, paving the way for novel personalised drug therapies to treat or prevent the deadly condition.

Researchers from Northeastern University in the US confirmed that one of those genes plays a causal role in cardiac hypertrophy – abnormal thickening of the heart muscle – which can lead to heart failure.

“This is an exciting direction for personalised medicine, and also for identifying genes and therapeutic targets for complex diseases that involve many genes,” said Alain Karma from Northeastern.

The ultimate goal is to create personalised therapeutic drugs to reverse heart disease.

The framework can also be used to predict whether individuals suffering from a particular disease will respond to a given drug treatment, said Marc Santolini, a postdoctoral research associate at Northeasterns Center for Complex Network Research.

“The method can predict beforehand whether a patient should be prescribed a different drug using just a simple blood test. This would save time and accelerate the therapy,” Santolini said.

In the traditional approach to find genes related to heart disease, researchers take donated hearts from people who died unexpectedly but were previously healthy.

They analyse the gene expression – the amount of messenger RNA and proteins – produced by the genes of healthy hearts and compare it with the gene expression of sick hearts explanted from end-stage heart failure patients undergoing heart transplant.

However, Karma said this method has not been very successful in finding important genes.

His team took a different approach – using the Hybrid Mouse Diversity Panel, a collection of 100 genetically different strains of mice that can be used to analyse the genetic and environmental factors underlying complex traits.

Within each strain, the mice are inbred, making them all identical twins on a genetic level.

Researchers took two mice from the same strain and gave one of them a stressor drug that induces heart failure.

They then compared the stressed mouses gene expression with its non-stressed twin.

Since the mice have the same genome, they were able to pinpoint individual genes that changed expression as a direct result of the heart stressor. The researchers identified 36 such genes.

Many of these genes were previously unknown to be implicated in heart failure. Karma said one of them is known as a transcription factor, meaning it controls the expression of many other genes.

The researchers confirmed the genes role by using molecular biology techniques to silence it and observe the resulting changes of expression.

They found the transcription factor gene was directly connected to a whole network of proteins known to play a role in cardiac hypertrophy.

One of the genes Karma found, called RFFL, was previously known to researchers to be implicated in other cardiac processes. However, it was not known to be related to hypertrophy.

As a next step, Karma said the new method could be tested on human stem cells, which have the same genetic code as the person they came from and can be induced to have similar gene expression patterns as heart cells.

“When you are comparing two populations of cells from the same person – one that has been controlled and one that has been under the effect of a drug or stressor – you can compare the change of gene expression in a personalised way,” Karma said.